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Maternal Genetic Variants of Digestive Diseases and Neural Tube Defects
Başlık:
Maternal Genetic Variants of Digestive Diseases and Neural Tube Defects
Yazar:
Hoang, Thanh T., author.
ISBN:
9780438179981
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (94 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: A.J. Agopian Committee members: Laura E. Mitchell; Shreela V. Sharma; Michael D. Swartz.
Özet:
Folic acid is known to prevent neural tube defects (NTDs); however, NTDs are also observed among women with adequate folic acid intake. Nutrient deficiencies via malabsorption may explain why women with adequate folic acid intake had offspring with a NTD. We examined the association between maternal genetic variants associated with digestive diseases that can lead to malabsorption, specifically lactase deficiency and celiac disease, and risk of NTDs.
We conducted a case-control study, using the National Birth Defects Prevention Study. This study included 667 case mothers and 743 control mothers with an estimated date of delivery of 1997-2009. Lactase deficiency was determined using rs4988235 and modeled recessively. Women with the CC genotype were considered lactase deficient, and women with the CT or TT genotype were not considered lactase deficient. The lactase analyses were conducted separately for non-Hispanic white (NHW) and Hispanic women, using logistic regression. We evaluated the potential effect modification by stratifying the analyses by lactose intake (<12 g/1,000 kcal vs ≥12 g/1,000 kcal). Maternal genetic variants-related to celiac disease were assessed using two different sets of variants. First, six genetic variants tagging for four human leukocyte antigens (HLAs) were used to categorize women into celiac risk groups (low, intermediate, or high). Second, fifteen additional non-HLA genetic variants (identified from genome wide association studies of celiac disease) were also examined individually and modeled additively. All analyses related to celiac disease were conducted using logistic regression, controlling for maternal race/ethnicity. Results from the non-HLA variants were adjusted for multiple comparisons, using false discovery rate.
From the lactase analyses, the odds of having the CC genotype were greater among cases compared to controls among NHW women (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of having the CC genotype were significantly lower among cases compared to controls (OR: 0.50; 95% CI: 0.33, 0.77). When stratified by lactose intake, the association with rs4988235 differed among NHWs but not Hispanics. There was no significant association between high versus low HLA celiac risk group and NTDs (aOR, 0.78; 95% CI, 0.46-1.32). Similarly, no significant association was observed between intermediate versus low HLA celiac risk group and NTDs (aOR, 1.03; 95% CI, 0.82-1.29). After adjusting for multiple comparisons, significant negative associations were observed with three non-HLA genetic variants (range of ORs: 0.69-0.81) and significant positive associations were observed with two non-HLA genetic variants (range of ORs: 1.27-1.73).
We are not aware of previous studies that have examined the association between maternal genetic markers of digestive diseases as a measurement of nutrient of malabsorption and NTDs in offspring. The results from this study contribute to improving our understanding of risk of NTDs among pregnant women with digestive diseases.
Notlar:
School code: 0219
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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XX(690289.1) | 690289-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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